CD44v6 High Membranous Expression Is a Predictive Marker of Therapy Response in Gastric Cancer Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Samples, Data Collection, and Tissue Microarray Preparation
2.2. CD44v6 Immunohistochemistry of GC Samples
2.3. Statistical Analysis
3. Results
3.1. Analysis of De Novo CD44v6 Membranous Expression and Its Relationship with GC Patients’ Survival
3.2. Analysis of CD44v6 Expression in Tumor Cells and Its Relationship with Therapy Response in GC Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables | Total No. Patients n = 326 | CD44v6_0 n = 68/326 (21%) | CD44v6_1+ n = 101/326 (31%) | CD44v6_2+ n = 68/326 (21%) | CD44v6_3+ n = 46/326 (14%) | CD44v6_4+ n = 43/326 (13%) | p-Value |
---|---|---|---|---|---|---|---|
Age (years) | >0.05 | ||||||
Mean | 67.7 | 68.0 | 67.5 | 66.2 | 69.9 | 69.9 | |
SD | 11.8 | 12.3 | 10.5 | 13.5 | 11.9 | 11.9 | |
Gender | 0.005 | ||||||
Male | 185 (56.7%) | 42 (61.8%) | 65 (64.4%) | 35 (51.5%) | 29 (63.0%) | 14 (32.6%) | |
Female | 141 (43.3%) | 26 (38.2%) | 36 (35.6%) | 33 (48.5%) | 17 (37.0%) | 29 (67.4%) | |
M:F ratio | 1.3:1 | 1.6:1 | 1.8:1 | 1.1:1 | 1.7:1 | 0.5:1 | |
Laurén classification | >0.05 | ||||||
Intestinal | 163 (50.0%) | 31 (45.6%) | 56 (55.4%) | 35 (51.5%) | 24 (52.2%) | 17 (39.5%) | |
Diffuse | 44 (13.5%) | 12 (17.6%) | 11 (10.9%) | 9 (13.2%) | 5 (10.9%) | 7 (16.3%) | |
Mixed | 84 (25.8%) | 18 (26.5%) | 18 (17.8%) | 18 (26.5%) | 15 (32.6%) | 15 (34.9%) | |
Indeterminate | 35 (10.7%) | 7 (10.3%) | 16 (15.8%) | 6 (8.8%) | 2 (4.3%) | 4 (9.3%) | |
Growth pattern | >0.05 | ||||||
Expansive | 60 (18.4%) | 13 (19.1%) | 19 (18.8%) | 12 (17.6%) | 10 (21.7%) | 6 (14.0%) | |
Infiltrative | 252 (77.3%) | 51 (75.0%) | 77 (76.2%) | 53 (77.9%) | 35 (76.1%) | 36 (83.7%) | |
Unclassified | 14 (4.3%) | 4 (5.9%) | 5 (5.0%) | 3 (4.4%) | 1 (2.2%) | 1 (2.3%) | |
Lymphatic permeation *1 | >0.05 | ||||||
Absent | 99 (30.5%) | 21 (30.9%) | 31 (31.0%) | 26 (38.8%) | 14 (30.4%) | 7 (16.3%) | |
Present | 225 (69.2%) | 47 (69.1%) | 69 (69.0%) | 41 (61.2%) | 32 (69.6%) | 36 (83.7%) | |
Perineural invasion *1 | 0.034 | ||||||
Absent | 166 (51.1%) | 34 (50.0%) | 59 (58.4%) | 38 (55.9%) | 22 (48.9%) | 13 (30.2%) | |
Present | 159 (48.9%) | 34 (50.0%) | 42 (41.6%) | 30 (44.1%) | 23 (51.1%) | 30 (69.8%) | |
Vascular invasion *1 | 0.005 | ||||||
Absent | 131 (40.6%) | 25 (37.3%) | 43 (42.6%) | 38 (56.7%) | 16 (35.6%) | 9 (20.9%) | |
Present | 192 (59.4%) | 42 (62.7%) | 58 (57.4%) | 29 (43.3%) | 29 (64.4%) | 34 (79.1%) | |
Surgical margins *1 | 0.007 | ||||||
R0 | 290 (89.2%) | 58 (85.3%) | 98 (98.0%) | 61 (89.7%) | 37 (80.4%) | 36 (83.7%) | |
R1/R2 | 35 (10.8%) | 10 (14.7%) | 2 (2.0%) | 7 (10.3%) | 9 (19.6%) | 7 (16.3%) | |
Depth of invasion (T) | 0.010 | ||||||
pT1 | 74 (22.7%) | 14 (20.6%) | 24 (23.8%) | 24 (35.3%) | 9 (19.6%) | 3 (7.0%) | |
pT2 | 41 (12.6%) | 6 (8.8%) | 14 (13.9%) | 41 (60.3%) | 10 (21.7%) | 8 (18.6%) | |
pT3–T4 | 211 (64.7%) | 48 (70.6%) | 63 (62.4%) | 3 (4.4%) | 27 (58.7%) | 32 (74.4%) | |
Lymph node metastases (N) *1 | >0.05 | ||||||
Absent (pN0) | 126 (38.8%) | 27 (39.7%) | 39 (39.0%) | 29 (42.6%) | 17 (37.0%) | 14 (32.6%) | |
Present (pN+) | 199 (61.2%) | 41 (60.3%) | 61 (61.0%) | 39 (57.4%) | 29 (63.0%) | 29 (67.4%) | |
Distant metastases (M) | >0.05 | ||||||
Absent | 257 (78.8%) | 48 (70.6%) | 89 (88.1%) | 51 (75.0%) | 35 (76.1%) | 34 (79.1%) | |
Present | 69 (21.2%) | 20 (29.4%) | 12 (11.9%) | 17 (25.0%) | 11 (23.9%) | 9 (20.9%) | |
TNM Staging | >0.05 | ||||||
I | 95 (29.1%) | 17 (25.0%) | 30 (29.7%) | 25 (36.8%) | 16 (34.8%) | 7 (16.3%) | |
II | 74 (22.7%) | 16 (23.5%) | 27 (26.7%) | 11 (16.2%) | 7 (15.2%) | 13 (30.2%) | |
III | 88 (27.0%) | 15 (22.1%) | 32 (31.7%) | 15 (22.1%) | 12 (26.1%) | 14 (32.6%) | |
IV | 69 (21.2%) | 20 (29.4%) | 12 (11.9%) | 17 (25.0%) | 11 (23.9%) | 9 (20.9%) |
Variables | Total No. Patients n = 638 | CD44v6_0 n = 58/638 (9%) | CD44v6_1+ n = 163/638 (26%) | CD44v6_2+ n = 194/638 (30%) | CD44v6_3+ n = 136/638 (21%) | CD44v6_4+ n = 87/638 (14%) | p-Value |
---|---|---|---|---|---|---|---|
Age (years) | >0.05 | ||||||
Mean | 60.8 | 59.5 | 60.8 | 60.2 | 60.7 | 63.3 | |
SD | 12.3 | 12.8 | 12.5 | 11.9 | 12.1 | 12.8 | |
Gender | 0.009 | ||||||
Male | 420 (65.8%) | 39 (67.2%) | 120 (73.6%) | 131 (67.5%) | 73 (53.7%) | 57 (65.5%) | |
Female | 218 (34.2%) | 19 (32.8%) | 43 (26.4%) | 63 (32.5%) | 63 (46.3%) | 30 (34.5%) | |
M:F ratio | 1.9:1 | 2.1:1 | 2.8:1 | 2.1:1 | 1.2:1 | 1.9:1 | |
Laurén classification *1 | >0.05 | ||||||
Intestinal | 299 (47.3%) | 26 (44.8%) | 67 (41.9%) | 102 (52.8%) | 64 (47.4%) | 40 (46.5%) | |
Diffuse | 239 (37.8%) | 29 (50.0%) | 68 (42.5%) | 58 (30.1%) | 51 (37.8%) | 33 (32.5%) | |
Mixed | 88 (13.9%) | 2 (3.4%) | 22 (13.8%) | 33 (17.1%) | 18 (13.3%) | 13 (15.1%) | |
Indeterminate *2 | 6 (0.9%) | 1 (1.7%) | 3 (1.9%) | 0 (0.0%) | 2 (1.5%) | 0 (0.0%) | |
Growth pattern | >0.05 | ||||||
Expansive | 65 (10.2%) | 6 (10.3%) | 17 (10.4%) | 20 (10.3%) | 13 (9.6%) | 9 (10.3%) | |
Infiltrative | 573 (89.8%) | 52 (89.7%) | 146 (89.6%) | 174 (89.7%) | 123 (90.4%) | 78 (89.7%) | |
Lymphatic permeation | 0.001 | ||||||
Absent | 309 (48.4%) | 28 (48.3%) | 82 (50.3%) | 99 (51.0%) | 76 (55.9%) | 24 (27.6%) | |
Present | 329 (51.6%) | 30 (51.7%) | 81 (49.7%) | 95 (49.0%) | 60 (44.1%) | 63 (72.4%) | |
Perineural invasion | >0.05 | ||||||
Absent | 405 (63.5%) | 27 (46.6%) | 103 (63.2%) | 130 (67.0%) | 88 (64.7%) | 57 (65.5%) | |
Present | 233 (36.5%) | 31 (53.4%) | 60 (36.8%) | 64 (33.0%) | 48 (35.3%) | 30 (34.5%) | |
Vascular invasion | >0.05 | ||||||
Absent | 536 (84.0%) | 48 (82.8%) | 133 (81.6%) | 168 (86.6%) | 114 (83.8%) | 73 (83.9%) | |
Present | 102 (16.0%) | 10 (17.2%) | 30 (18.4%) | 26 (13.4%) | 22 (16.2%) | 14 (16.1%) | |
Surgical margins *3 | |||||||
R0 | 638 (100%) | 58 (100%) | 163 (100%) | 194 (100%) | 136 (100%) | 87 (100%) | |
R1/R2 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | |
Depth of invasion (T) | 0.0001 | ||||||
pT1 | 212 (33.2%) | 11 (19.0%) | 53 (32.5%) | 83 (42.8%) | 45 (33.1%) | 20 (23.0%) | |
pT2 | 118 (18.5%) | 7 (12.1%) | 23 (14.1%) | 39 (20.1%) | 33 (24.3%) | 16 (18.4%) | |
pT3–T4 | 308 (48.3%) | 40 (69.0%) | 87 (53.4%) | 72 (37.1%) | 58 (42.6%) | 51 (58.6%) | |
Lymph node metastases (N) | 0.008 | ||||||
Absent (pN0) | 324 (50.8%) | 25 (43.1%) | 79 (48.5%) | 113 (58.2%) | 75 (55.1%) | 32 (36.8%) | |
Present (pN+) | 314 (49.2%) | 33 (56.9%) | 84 (51.5%) | 81 (41.8%) | 61 (44.9%) | 55 (63.2%) | |
Distant metastases(M) | >0.05 | ||||||
Absent | 596 (93.4%) | 52 (89.7%) | 153 (93.9%) | 186 (95.9%) | 125 (91.9%) | 80 (92.0%) | |
Present | 42 (6.6%) | 6 (10.3%) | 10 (6.1%) | 8 (4.1%) | 11 (8.1%) | 7 (8.0%) | |
TNM Staging | 0.001 | ||||||
I | 269(42.2%) | 15 (25.9%) | 62 (38.0%) | 106 (54.6%) | 63 (46.3%) | 23 (26.4%) | |
II | 158 (24.8%) | 16 (27.6%) | 45 (27.6%) | 36 (18.6%) | 34 (25.0%) | 27 (31.0%) | |
III | 170 (26.6%) | 21 (36.2%) | 46 (28.2%) | 44 (22.7%) | 28 (20.6%) | 31 (35.6%) | |
IV | 41 (6.4%) | 6 (10.3%) | 10 (6.1%) | 8 (4.1%) | 11 (8.1%) | 6 (6.9%) |
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Almeida, G.M.; Pereira, C.; Park, J.-H.; Lemos, C.; Campelos, S.; Gullo, I.; Martins, D.; Gonçalves, G.; Leitão, D.; Neto, J.L.; et al. CD44v6 High Membranous Expression Is a Predictive Marker of Therapy Response in Gastric Cancer Patients. Biomedicines 2021, 9, 1249. https://doi.org/10.3390/biomedicines9091249
Almeida GM, Pereira C, Park J-H, Lemos C, Campelos S, Gullo I, Martins D, Gonçalves G, Leitão D, Neto JL, et al. CD44v6 High Membranous Expression Is a Predictive Marker of Therapy Response in Gastric Cancer Patients. Biomedicines. 2021; 9(9):1249. https://doi.org/10.3390/biomedicines9091249
Chicago/Turabian StyleAlmeida, Gabriela M, Carla Pereira, Ji-Hyeon Park, Carolina Lemos, Sofia Campelos, Irene Gullo, Diana Martins, Gilza Gonçalves, Dina Leitão, João Luís Neto, and et al. 2021. "CD44v6 High Membranous Expression Is a Predictive Marker of Therapy Response in Gastric Cancer Patients" Biomedicines 9, no. 9: 1249. https://doi.org/10.3390/biomedicines9091249